Nitrogen dioxide, a common air pollutant, has been shown to react with amines to yield N-nitrosamines. The majority to N-nitrosamines are potent carcinogens which have been shown to induce tumors in a wide variety of species and tissues. Much evidence indicates that this class of compounds is carcinogenic in humans as well. Significant sources of exposure to nitrosamines appear to occur from formation in vivo due to ingested or inhaled nitrogen oxides. The experiments described in this proposal are directed at measuring the amounts of nitrosamines that are formed in the lung as a result of nitrogen oxide inhalation. These definitive studies will employ an isolated perfused lung system in order to eliminate the possibility of competing acid-catalyzed nitrosation reactions in the stomach. Ambiguous results were obtained in previous studies in vivo because of the likelihood of such competing reactions. The kinetics of nitrosation will be evaluated in an attempt to elucidate the probable mechanism of nitrosamine formation and to help develop a predictive model of exposure. Kinetic studies will characterize the formation of both carcinogenic and noncarcinogenic nitrosamines from the reaction of nitrogen oxides with amine precursors of varying structure, in order to determine the relationship between the sstructure of the amine and rate of nitrosation. The effectiveness of several known nitrosation inhibitors at preventing nitrosation in the ling will also be determined. The effects of altering the structure and hydrophobicity of both the amine precursor and inhibitor on the rate of nitrosation will be compared to the results of simple chemical modesl and in vivo exposures as a means of elucidating the probable mechanism of nitrosation in vivo. The data acquired in the course of these experiments will find practical application in the setting of air quality standards and possibly in drug inhalation therapy.